Chromoprotein enediyne antibiotics

The similarities of the core enediynes of the kedarcidin and C-1027 chromophores with the neocarzinostatin chromophore structure means that many of the synthetic studies relating to NCS chromophore also, by implication, relate to the other chromoprotein enediyne antibiotics, although no examples specifically relating to these new antibiotics have appeared to date. However, a synthesis of kedarosamine, a sugar component of the kedarcidin chromophore, has appeared recently [272],... 

The tightly bound chromophore could be extracted from the protein with methanol [186], and the major component of the extract was determined to have the enediyne structure 116 (Figure 11.21), related to chromophores of other chromoprotein antitumor agents such as neocarzinostatin. Additional minor components were extracted, variously containing an OH group instead of OMe attached to the enediyne core, with Cl instead of OMe when chloride was present in the buffer salt, or with OEt instead of OMe when ethanol was used for the extraction. Another byproduct was isolated in the form of structure 117, consistent with a facile cy-doaromatization reaction as observed for all other enediyne antibiotics. Surprisingly, 117 also displayed antibiotic and antitumor activity, perhaps due to alkylation of DNA or protein by the aziridine. The interpretation of these results was that 116 and the other enediyne byproducts were merely artifacts of the extraction procedure and that the true structure of the maduropeptin chromophore is the aziridine 118. 

Maduropeptin is a complex of new chromoprotein antitumor antibiotics isolated from Ac-tinomadura madurae (ATCC 39144) in 1990 [35, 36], It exhibits potent inhibitory activity against Gram-positive bacteria and tumor cells and strong in-vivo antitumor activity in P388 leukemia and B16 melanoma implanted mice. The structure of the chromophore has been recently elucidated [36], confirming it as a member of the family of enediyne antibiotics, and will be published shortly. 

Enediynes. - Several enediyne anti-tumour antibiotics have been isolated from Streptomyces species, including the chromoprotein C-1027, which consists of a DNA-cleaving enediyene chromophore and carrier apoprotein. The room temperature powder spectrum of C-1027 contains stable signals from species at g = 2.003 and 2.01, attributed to an aryl radical derived from the chromophore and a glycine peroxyl radical centred on the apoprotein, respectively. These radicals are believed to be involved in the self-inactivation of C-1027, which is initiated by a biradical (p-benzyne) form of the parent enediyne. ... 

Neocarzinostatin (NCS) is an enediyne chromoprotein antibiotic secreted by Streptomyces macromomyceticus with potent antibacterial and antitumor activities. NCS is composed of the NCS chromophore (Scheme 57.16) and a carrier apoprotein. Enantiopure tra s-4,5-dioxygenated cyclopent-2-enone (—)-63 can be used as a building block... 

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